Further, chronic

lithium treatment, which began on day 11 after the first taxol injection, reversed the existing mechanical and thermal allodynia induced by taxol. The taxol-induced increased GSK3 beta activities and decreased AKT and mTOR activities in the spinal dorsal horn were also reversed by lithium. Meanwhile, protein expressions of GLT-1, GFAP and IL-1 beta in the spinal dorsal horn were improved. Hence, suppression of spinal GSK3 beta activities is a key mechanism used by lithium to reduce taxol-induced selleck products neuropathic pain, and targeting spinal GSK3 beta is an effective approach to ameliorate GLT-1 expression and suppress the activation of astrocytes and IL-1 beta over-production in the spinal dorsal horn. Published by Elsevier Ltd. on behalf of IBRO.”
“Morphological changes that occur during kidney injury involve actin skeleton remodeling. Here we tested whether heat-shock protein 27 (HSP27), a small stress response protein involved in cytoskeletal remodeling, protects the kidney from tubulointerstitial fibrosis in Anlotinib supplier obstructive nephropathy. Tubular cell HSP27 immunostaining was significantly increased in human kidneys with ureteropelvic junction obstruction, supporting the clinical relevance of our studies. To develop an animal model for mechanistic

studies, we generated transgenic mice that specifically overexpress human HSP27 in renal tubules, under the kidney androgen-regulated protein promoter, and determined the effects of H5P27 overexpression on epithelial-to-mesenchymal transition and tubulointerstitial fibrosis following unilateral ureteral obstruction. This was associated with decreased fibrogenesis as evidenced by significant new declines in phosphorylated p38MAPK, collagen III, alpha-smooth

muscle actin, 4-hydroxynonenal, and reduced trichrome staining following obstruction. Notably, E-cadherin and beta-catenin remained at the cell membrane of tubular cells in transgenic mice with an obstructed ureter. Monocyte/macrophage infiltration, however, was not significantly affected in these transgenic mice. Thus, tubular HSP27 inhibits fibrogenesis in obstructive nephropathy. Further studies are needed to determine pathways regulating the interactions between HSP27 and the E-cadherin-beta-catenin complex. Kidney International (2012) 83, 84-92; doi:10.1038/ki.2012.336; published online 12 September 2012″
“Nerve growth factor (NGF) augments the excitability of isolated rat sensory neurons through activation of the p75 neurotrophin receptor (p75(NTR)) and its downstream sphingomyelin signaling cascade, wherein neutral sphingomyelinase(s) (nSMase), ceramide, and the atypical protein-kinase C (aPKC), protein-kinase M zeta (PKM zeta), are key mediators. Here we examined these same receptor-pathways in vivo for their role in mechanical hyperalgesia from exogenous NGF.